It is generally accepted that the afferent and efferent arterioles of the glomerulus play a major role in determining the total renal vascular resistance and glomerular filtration rate. Although it is clear that these processes are under the control of numerous vasoactive compounds, the renal vascular sites of action of these substances are either unknown or remain controversial. This uncertainty is largely due to the inaccessibility of the small resistance vessels of the kidney for direct study. Recently, a technique has been developed in this laboratory that permits the study of individual renal arterioles in vitro, free from uncontrolled systemic hemodynamic and hormonal influences. The technique is a modification of the isolated perfused tubule methodology in which changes in lumen diameter of a single isolated arteriole in response to a vasoactive agent can be directly measured. Using this technique the sites at which various vasoactive compounds act and interact to regulate renal hemodynamics at the arteriolar level will be determined. The proposed research will focus on the following specific aims; 1) To determine the role of angiotensin in the regulation of arteriolar tone. This includes determining the sites of action of angiotensin II, the pharmacological characterization of angiotensin receptors in normal, high and low renin states and the role of the endothelium in the conversion of angiotensin I to angiotensin II; 2) To determine the role of prostaglandins in the control of arteriolar tone. This includes determining the major prostaglandins synthesized by renal microvessels, the vascular sites of action of exogenous and endogenously produced prostaglandins and the role of arachidonic acid metabolites in the vasodilation produced by acetylcholine and bradykinin; 3) To determine the role of other vasoactive compounds that are thought to be important in the regulation of arteriolar resistance. This includes determining the site of action and receptor characterization of alpha and beta adrenergics, dopamine, acetylcholine and bradykinin. The above studies will be performed on isolated interlobular arteries and afferent and efferent arterioles from both superficial and juxtamedullary glomeruli. It is the long term objective of these studies to gain a better understanding of the physiologic factors that regulate renal arteriolar resistance in normal and pathologic states.